Heterocyclic amine derivatives

Abstract

The present invention relates to compounds of formula I wherein A, B, X, Y, Ar, R 1 , R 2 , R′, m and n are as defined herein and to pharmaceutical active acid addition salts thereof, which have a good affinity to the trace amine associated receptors TAAR1, so that they can be used for the treatment of depression, anxiety disorders and bipolar disorder.

The invention claimed is: 
     
       1. A compound of formula I 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is hydrogen, lower alkyl, halogen, lower alkyl substituted by halogen, lower alkoxy,
 lower alkoxy substituted by halogen, cyano, nitro, C 3-6 -cycloalkyl, —CH 2 —C 3-6 -cycloalkyl, 
 —O—CH 2 —C 3-6 -cycloalkyl, —O—(CH 2 ) 2 —O-lower alkyl, S(O) 2 CH 3 , SF 5 , —C(O)NH-lower alkyl, phenyl, —O-pyrimidinyl, optionally substituted by lower alkoxy substituted by halogen, or is benzyl, oxetanyl or furanyl; 
 
         m is 1 or 2; 
         Ar is aryl or heteroaryl, selected from the group consisting of naphthyl, pyrimidinyl, benzothiazolyl, quinolinyl, quinazolinyl, benzo[d][1.3]dioxolyl, 5,6,7,8-tetrahydro-quinazolinyl, pyrazolyl, pyrazinyl, pyridazinyl, and 1,3,4-oxadiazolyl; 
         Y is a bond, —CH 2 —, —CH 2 CH 2 —, —CH(CF 3 )— or —CH(CH 3 )—; 
         R 2  is hydrogen or lower alkyl; 
         A is CR or N; and R is hydrogen, cyano, halogen or lower alkyl; 
         R′ is hydrogen or halogen; with the proviso that when R′ is halogen, A is CH; 
         B is CH or N; 
         n is o, 1 or 2; and 
         X is a bond, —CH 2 — or —O—; 
         or a pharmaceutical active acid addition salt thereof. 
       
     
     
       2. The compound of  claim 1 , having formula IA 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is hydrogen, lower alkyl, halogen, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by halogen, cyano, nitro, C 3-6 -cycloalkyl, S(O) 2 CH 3  or phenyl; 
         m is 1 or 2; 
         Ar is aryl or heteroaryl, selected from the group consisting of naphthyl, pyrimidinyl, benzothiazolyl, quinolinyl, quinazolinyl, benzo[d][1.3]dioxolyl, 5,6,7,8-tetrahydro-quinazolinyl, pyrazolyl and 1,3,4-oxadiazolyl; 
         Y is a bond, —CH 2 —, —CH 2 CH 2 —, —CH(CF 3 )— or —CH(CH 3 )—; 
         R 2  is hydrogen or lower alkyl; 
         A is CR or N; and R is hydrogen, cyano, halogen or lower alkyl; 
         B is CH or N; 
         n is o, 1 or 2; and 
         X is a bond, —CH 2 — or —O—; 
         or a pharmaceutical active acid addition salt thereof. 
       
     
     
       3. The compound of  claim 1 , wherein A is CR, and B is CH. 
     
     
       4. The compound of  claim 3 , wherein Y is a bond and Ar is naphthyl. 
     
     
       5. The compound of  claim 4 , wherein said compound is
 ((S)-4-Morpholin-2-yl-phenyl)-naphthalen-2-yl-amine 
 or a pharmaceutical active acid addition salt thereof. 
 
     
     
       6. The compound of  claim 3 , wherein Y is a bond and Ar is pyrimidinyl, pyrazolyl, benzothiazolyl, quinolinyl, quinazolinyl, benzo[d][1.3]dioxolyl, 5,6,7,8-tetrahydro-quinazolinyl, pyrazinyl, pyridazinyl or 1,3,4-oxadiazolyl. 
     
     
       7. The compound of  claim 6 , selected from the group consisting of
 (RS)-(4,6-Dimethyl-pyrimidin-2-yl)-(4-pyrrolidin-3-yl-phenyl)-amine; hydrochloride; 
 (RS)-(5-Chloro-pyrimidin-2-yl)-(4-morpholin-2-yl-phenyl)-amine; 
 (RS)-(5-Bromo-pyrimidin-2-yl)-(4-morpholin-2-yl-phenyl)-amine; 
 (5-Methoxy-pyrimidin-2-yl)-((S)-4-morpholin-2-yl-phenyl)-amine; 
 (5-Fluoro-pyrimidin-2-yl)-((S)-4-morpholin-2-yl-phenyl)-amine; 
 (5-Ethyl-pyrimidin-2-yl)-((S)-4-morpholin-2-yl-phenyl)-amine; and 
 2-((S)-4-Morpholin-2-yl-phenylamino)-pyrimidine-5-carbonitrile, 
 or a pharmaceutical active acid addition salt thereof. 
 
     
     
       8. The compound of  claim 6 , selected from the group consisting of
 (5-Cyclopropyl-pyrimidin-2-yl)-((S)-4-morpholin-2-yl-phenyl)-amine; 
 (5-Methyl-pyrimidin-2-yl)-((S)-4-morpholin-2-yl-phenyl)-amine; 
 ((S)-4-Morpholin-2-yl-phenyl)-(5-trifluoromethyl-pyrimidin-2-yl)-amine; 
 ((S)-4-Morpholin-2-yl-phenyl)-(5-propyl-pyrimidin-2-yl)-amine; 
 (6-Chloro-benzothiazol-2-yl)-((S)-4-morpholin-2-yl-phenyl)-amine; and 
 (5-Ethoxy-pyrimidin-2-yl)-((S)-4-morpholin-2-yl-phenyl)-amine; 
 or a pharmaceutical active acid addition salt thereof. 
 
     
     
       9. The compound of  claim 6 , selected from the group consisting of
 ((S)-4-Morpholin-2-yl-phenyl)-quinolin-2-yl-amine; 
 (S)-6-Chloro-N-(4-(morpholin-2-yl)phenyl)quinolin-2-amine; 
 (S)-2-Methyl-N-(4-(morpholin-2-yl)phenyl)quinolin-8-amine; 
 (S)—N-(4-(Morpholin-2-yl)phenyl)-2,8-bis(trifluoromethyl)quinolin-4-amine; 
 (S)-6-Chloro-N-(4-(morpholin-2-yl)phenyl)quinazolin-4-amine; 
 (S)-8-Chloro-N-(4-(morpholin-2-yl)phenyl)quinolin-2-amine; 
 (S)-5-Bromo-N-(4-(morpholin-2-yl)phenyl)quinolin-2-amine; and 
 (S)-4-Chloro-N-(4-(morpholin-2-yl)phenyl)quinolin-2-amine; 
 or a pharmaceutical active acid addition salt thereof. 
 
     
     
       10. The compound of  claim 6 , selected from the group consisting of
 (S)—N-(4-(Morpholin-2-yl)phenyl)benzo[d][1,3]dioxol-5-amine; and 
 (S)-5-Bromo-N-(4-(morpholin-2-yl)phenyl)quinolin-8-amine; 
 or a pharmaceutical active acid addition salt thereof. 
 
     
     
       11. The compound of  claim 6 , selected from the group consisting of
 (R)-5-Ethyl-N-(4-(morpholin-2-yl)phenyl)pyrimidin-2-amine; 
 (5-Ethyl-4-methyl-pyrimidin-2-yl)-((S)-4-morpholin-2-yl-phenyl)-amine; 
 (5-Isopropyl-4-methyl-pyrimidin-2-yl)-((S)-4-morpholin-2-yl-phenyl)-amine; 
 ((S)-4-Morpholin-2-yl-phenyl)-(5,6,7,8-tetrahydro-quinazolin-2-yl)-amine; and 
 ((S)-4-Morpholin-2-yl-phenyl)-(5-nitro-pyrimidin-2-yl)-amine; 
 or a pharmaceutical active acid addition salt thereof. 
 
     
     
       12. The compound of  claim 6 , selected from the group consisting of
 (5-Methanesulfonyl-pyrimidin-2-yl)-((S)-4-morpholin-2-yl-phenyl)-amine; 
 (RS)-(5-Chloro-pyrimidin-2-yl)-(2-methyl-4-morpholin-2-yl-phenyl)-amine; 
 (5-Cyclopropyl-pyrimidin-2-yl)-((R)-4-morpholin-2-yl-phenyl)-amine; 
 (RS)-5-Cyclopropyl-N-(2-methyl-4-(morpholin-2-yl)phenyl)pyrimidin-2-amine; and 
 (RS)-5-Ethyl-N-(2-methyl-4-(morpholin-2-yl)phenyl)pyrimidin-2-amine; 
 or a pharmaceutically suitable acid addition salt thereof. 
 
     
     
       13. The compound of  claim 6 , selected from the group consisting of
 (RS)-5-Bromo-N-(2-methyl-4-(morpholin-2-yl)phenyl)pyrimidin-2-amine; 
 ((R)-4-Morpholin-2-yl-phenyl)-(5-propyl-pyrimidin-2-yl)-amine; 
 (5-Bromo-pyrimidin-2-yl)-((R)-4-morpholin-2-yl-phenyl)-amine; 
 ((R)-4-Morpholin-2-yl-phenyl)-(5-trifluoromethyl-pyrimidin-2-yl)-amine; 
 (RS)-5-Chloro-N-(2-fluoro-4-(morpholin-2-yl)phenyl)pyrimidin-2-amine; 
 (RS)-5-Ethyl-N-(2-fluoro-4-(morpholin-2-yl)phenyl)pyrimidin-2-amine; 
 (RS)-5-Cyclopropyl-N-(2-fluoro-4-(morpholin-2-yl)phenyl)pyrimidin-2-amine; 
 (RS)-(5-Ethoxy-pyrimidin-2-yl)-(2-fluoro-4-morpholin-2-yl-phenyl)-amine; and 
 (RS)-(2-Fluoro-4-morpholin-2-yl-phenyl)-(5-propyl-pyrimidin-2-yl)-amine; 
 or a pharmaceutically suitable acid addition salt thereof. 
 
     
     
       14. The compound of  claim 6 , selected from the group consisting of
 (RS)-(5-Bromo-pyrimidin-2-yl)-(2-fluoro-4-morpholin-2-yl-phenyl)-amine; 
 (R)-5-Chloro-N-(4-(morpholin-2-yl)phenyl)pyrimidin-2-amine; 
 (S)-5-Chloro-N-(4-(morpholin-2-yl)phenyl)pyrimidin-2-amine; 
 (5-Ethoxy-pyrimidin-2-yl)-((R)-4-morpholin-2-yl-phenyl)-amine; 
 (5-Ethyl-pyrimidin-2-yl)-((R)-2-methyl-4-morpholin-2-yl-phenyl)-amine; 
 (5-Ethyl-pyrimidin-2-yl)-((S)-2-methyl-4-morpholin-2-yl-phenyl)-amine; 
 (5-Cyclopropyl-pyrimidin-2-yl)-((R)-2-methyl-4-morpholin-2-yl-phenyl)-amine; 
 (5-Cyclopropyl-pyrimidin-2-yl)-((S)-2-methyl-4-morpholin-2-yl-phenyl)-amine; 
 (5-Ethyl-pyrimidin-2-yl)-((S)-4-piperidin-3-yl-phenyl)-amine; and 
 (S)—N-(4-(Morpholin-2-yl)phenyl)-5-phenyl-1H-pyrazol-3-amine; 
 or a pharmaceutically suitable acid addition salt thereof. 
 
     
     
       15. The compound of  claim 6 , selected from the group consisting of
 (5-Ethoxy-pyrimidin-2-yl)-((S)-4-piperidin-3-yl-phenyl)-amine; 
 (S)—N-(4-(Morpholin-2-yl)phenyl)-5-phenyl-1,3,4-oxadiazol-2-amine; 
 (5-Ethyl-pyrimidin-2-yl)-((R)-2-fluoro-4-morpholin-2-yl-phenyl)-amine; 
 (5-Ethyl-pyrimidin-2-yl)-((S)-2-fluoro-4-morpholin-2-yl-phenyl)-amine; 
 (5-Cyclopropyl-pyrimidin-2-yl)-((R)-2-fluoro-4-morpholin-2-yl-phenyl)-amine; 
 (5-Cyclopropyl-pyrimidin-2-yl)-((S)-2-fluoro-4-morpholin-2-yl-phenyl)-amine; 
 (RS)-(2-Fluoro-4-morpholin-2-yl-phenyl)-(5-trifluoromethyl-pyrimidin-2-yl)-amine; 
 (5-Isopropoxy-pyrimidin-2-yl)-((S)-4-morpholin-2-yl-phenyl)-amine; 
 (5-Isopropoxy-pyrimidin-2-yl)-((R)-4-morpholin-2-yl-phenyl)-amine; and 
 (S)-5-(Cyclopropylmethoxy)-N-(4-(morpholin-2-yl)phenyl)pyrimidin-2-amine; 
 or a pharmaceutically suitable acid addition salt thereof. 
 
     
     
       16. The compound of  claim 6 , selected from the group consisting of
 (R)-5-(Cyclopropylmethoxy)-N-(4-(morpholin-2-yl)phenyl)pyrimidin-2-amine; 
 (5-Bromo-pyrimidin-2-yl)-((R)-2-fluoro-4-morpholin-2-yl-phenyl)-amine; 
 (5-Bromo-pyrimidin-2-yl)-((S)-2-fluoro-4-morpholin-2-yl-phenyl)-amine; 
 ((R)-2-Fluoro-4-morpholin-2-yl-phenyl)-(5-propyl-pyrimidin-2-yl)-amine; 
 ((S)-2-Fluoro-4-morpholin-2-yl-phenyl)-(5-propyl-pyrimidin-2-yl)-amine; 
 (5-Chloro-pyrimidin-2-yl)-((R)-2-fluoro-4-morpholin-2-yl-phenyl)-amine; (5-Chloro-pyrimidin-2-yl)-((S)-2-fluoro-4-morpholin-2-yl-phenyl)-amine; 
 (5-Ethoxy-pyrimidin-2-yl)-((R)-2-fluoro-4-morpholin-2-yl-phenyl)-amine; 
 (5-Ethoxy-pyrimidin-2-yl)-((S)-2-fluoro-4-morpholin-2-yl-phenyl)-amine; and 
 ((R)-2-Fluoro-4-morpholin-2-yl-phenyl)-(5-trifluoromethyl-pyrimidin-2-yl)-amine; 
 or a pharmaceutically suitable acid addition salt thereof. 
 
     
     
       17. The compound of  claim 6 , selected from the group consisting of
 ((S)-2-Fluoro-4-morpholin-2-yl-phenyl)-(5-trifluoromethyl-pyrimidin-2-yl)-amine; 
 ((S)-4-Morpholin-2-yl-phenyl)-[5-(2,2,2-trifluoro-ethoxy)-pyrimidin-2-yl]-amine; 
 ((R)-4-Morpholin-2-yl-phenyl)-[5-(2,2,2-trifluoro-ethoxy)-pyrimidin-2-yl]-amine; 
 [5-(2-Methoxy-ethoxy)-pyrimidin-2-yl]-((S)-4-morpholin-2-yl-phenyl)-amine; 
 [5-(2-Methoxy-ethoxy)-pyrimidin-2-yl]-((R)-4-morpholin-2-yl-phenyl)-amine; 
 (RS)-(1-Methyl-1H-pyrazol-3-yl)-(4-morpholin-2-yl-phenyl)-amine; 
 (RS)-(4-Bromo-1-methyl-1H-pyrazol-3-yl)-(4-morpholin-2-yl-phenyl)-amine; 
 ((R)-2-Fluoro-4-morpholin-2-yl-phenyl)-[5-(2,2,2-trifluoro-ethoxy)-pyrimidin-2-yl]-amine; 
 ((S)-2-Fluoro-4-morpholin-2-yl-phenyl)-[5-(2,2,2-trifluoro-ethoxy)-pyrimidin-2-yl]-amine; and 
 (RS)-(1-Cyclopropylmethyl-1H-pyrazol-3-yl)-(4-morpholin-2-yl-phenyl)-amine; 
 or a pharmaceutically suitable acid addition salt thereof. 
 
     
     
       18. The compound of  claim 6 , selected from the group consisting of
 (5-Furan-2-yl-pyrimidin-2-yl)-((S)-4-morpholin-2-yl-phenyl)-amine; 
 (5-Furan-2-yl-pyrimidin-2-yl)-((R)-4-morpholin-2-yl-phenyl)-amine; 
 (RS)—N-(2-Chloro-4-(morpholin-2-yl)phenyl)-5-cyclopropylpyrimidin-2-amine; 
 (RS)-[1-(2,2-Difluoro-ethyl)-1H-pyrazol-3-yl]-(4-morpholin-2-yl-phenyl)-amine; 
 ((R)-2-Fluoro-4-morpholin-2-yl-phenyl)-[5-(2-methoxy-ethoxy)-pyrimidin-2-yl]-amine; 
 ((S)-2-Fluoro-4-morpholin-2-yl-phenyl)-[5-(2-methoxy-ethoxy)-pyrimidin-2-yl]-amine; 
 ((S)-4-Morpholin-2-yl-phenyl)-(2-trifluoromethyl-pyrimidin-5-yl)-amine; 
 ((R)-4-Morpholin-2-yl-phenyl)-(2-trifluoromethyl-pyrimidin-5-yl)-amine; 
 (RS)-(4-Morpholin-2-yl-phenyl)-(1H-pyrazol-3-yl)-amine; and 
 (5-Methyl-pyrazin-2-yl)-((S)-4-morpholin-2-yl-phenyl)-amine; 
 or a pharmaceutically suitable acid addition salt thereof. 
 
     
     
       19. The compound of  claim 6 , selected from the group consisting of
 (5-Methyl-pyrazin-2-yl)-((R)-4-morpholin-2-yl-phenyl)-amine; 
 2-((S)-4-Morpholin-2-yl-phenylamino)-pyrimidine-5-carboxylic acid methylamide; 
 2-((R)-4-Morpholin-2-yl-phenylamino)-pyrimidine-5-carboxylic acid methylamide; 
 (6-Methyl-pyridazin-3-yl)-((S)-4-morpholin-2-yl-phenyl)-amine; 
 (1-Benzyl-1H-pyrazol-3-yl)-((S)-4-morpholin-2-yl-phenyl)-amine; 
 (1-Benzyl-1H-pyrazol-3-yl)-((R)-4-morpholin-2-yl-phenyl)-amine; 
 ((S)-4-Morpholin-2-yl-phenyl)-(1-phenyl-1H-pyrazol-3-yl)-amine; 
 ((R)-4-Morpholin-2-yl-phenyl)-(1-phenyl-1H-pyrazol-3-yl)-amine; and 
 ((R)-2-Methyl-4-morpholin-2-yl-phenyl)-(5-trifluoromethyl-pyrimidin-2-yl)-amine; 
 or a pharmaceutically suitable acid addition salt thereof. 
 
     
     
       20. The compound of  claim 6 , selected from the group consisting of
 ((S)-2-Methyl-4-morpholin-2-yl-phenyl)-(5-trifluoromethyl-pyrimidin-2-yl)-amine; 
 ((R)-2-Chloro-4-morpholin-2-yl-phenyl)-(5-trifluoromethyl-pyrimidin-2-yl)-amine; 
 ((S)-2-Chloro-4-morpholin-2-yl-phenyl)-(5-trifluoromethyl-pyrimidin-2-yl)-amine; 
 (R)—N-(2-Chloro-4-(morpholin-2-yl)phenyl)-5-cyclopropylpyrimidin-2-amine; 
 (S)—N-(2-Chloro-4-(morpholin-2-yl)phenyl)-5-cyclopropylpyrimidin-2-amine; 
 ((R)-4-Morpholin-2-yl-phenyl)-[4-(2,2,2-trifluoro-ethoxy)-pyrimidin-2-yl]-amine; 
 (R)—N-(4-(Morpholin-2-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amine; 
 (R)-5-(5-(Difluoromethoxy)pyrimidin-2-yloxy)-N-(4-(morpholin-2-yl)phenyl)pyrimidin-2-amine; and 
 (R)—N-(2-Chloro-4-(morpholin-2-yl)phenyl)-5-(5-(difluoromethoxy)pyrimidin-2-yloxy)pyrimidin-2-amine; 
 or a pharmaceutically suitable acid addition salt thereof. 
 
     
     
       21. The compound of  claim 6 , selected from the group consisting of
 (R)—N-(4-(Morpholin-2-yl)phenyl)pyrimidin-2-amine; 
 ((R)-4-Morpholin-2-yl-phenyl)-quinazolin-2-yl-amine; 
 (4-Methyl-6-trifluoromethyl-pyrimidin-2-yl)-((R)-4-morpholin-2-yl-phenyl)-amine; 
 (R)-5-(Difluoromethoxy)-N-(4-(morpholin-2-yl)phenyl)pyrimidin-2-amine; 
 (4-Chloro-6-methoxy-pyrimidin-2-yl)-((R)-4-morpholin-2-yl-phenyl)-amine; 
 2-((R)-4-Morpholin-2-yl-phenylamino)-pyrimidine-4-carbonitrile; 
 (4,6-Dimethyl-pyrimidin-2-yl)-((R)-4-morpholin-2-yl-phenyl)-amine; 
 (4,6-Dimethoxy-pyrimidin-2-yl)-((R)-4-morpholin-2-yl-phenyl)-amine; and 
 ((R)-2-Chloro-4-morpholin-2-yl-phenyl)-[5-(2,2,2-trifluoro-ethoxy)-pyrimidin-2-yl]-amine; 
 or a pharmaceutically suitable acid addition salt thereof. 
 
     
     
       22. The compound of  claim 6 , selected from the group consisting of
 (S)-2,5-Dichloro-N-(4-(morpholin-2-yl)phenyl)pyrimidin-4-amine; 
 ((S)-4-Morpholin-2-yl-phenyl)-[4-(2,2,2-trifluoro-ethoxy)-pyrimidin-2-yl]-amine; 
 [5-Fluoro-4-(2,2,2-trifluoro-ethoxy)-pyrimidin-2-yl]-((R)-4-morpholin-2-yl-phenyl)-amine; 
 (4-Cyclopropyl-pyrimidin-2-yl)-((R)-4-morpholin-2-yl-phenyl)-amine; 
 (4-Cyclopropyl-5-fluoro-pyrimidin-2-yl)-((R)-4-morpholin-2-yl-phenyl)-amine; 
 (R)-5-Cyclopropyl-N-(3-fluoro-4-(morpholin-2-yl)phenyl)pyrimidin-2-amine; 
 ((S)-3-Chloro-4-morpholin-2-yl-phenyl)-(5-cyclopropyl-pyrimidin-2-yl)-amine; 
 ((R)-3-Chloro-4-morpholin-2-yl-phenyl)-(5-cyclopropyl-pyrimidin-2-yl)-amine; and 
 (S)-5-Cyclopropyl-N-(3-fluoro-4-(morpholin-2-yl)phenyl)pyrimidin-2-amine; 
 or a pharmaceutically suitable acid addition salt thereof. 
 
     
     
       23. The compound of  claim 6 , selected from the group consisting of (R)—N-(3-Fluoro-4-(morpholin-2-yl)phenyl)-5-(trifluoromethyl)pyrimidin-2-amine;
 (S)—N-(3-Fluoro-4-(morpholin-2-yl)phenyl)-5-(trifluoromethyl)pyrimidin-2-amine; 
 (R)—N-(4-(Morpholin-2-yl)phenyl)-6-(trifluoromethyl)pyrimidin-4-amine; 
 (R)-6-Chloro-N-(4-(morpholin-2-yl)phenyl)pyrimidin-4-amine; 
 (R)—N-(4-(morpholin-2-yl)phenyl)-2-(trifluoromethyl)pyrimidin-4-amine; 
 (R)—N-(4-(Morpholin-2-yl)phenyl)-5-(trifluoromethyl)pyrazin-2-amine; 
 ((R)-3-Chloro-4-morpholin-2-yl-phenyl)-(5-chloro-pyrimidin-2-yl)-amine; 
 ((R)-3-Chloro-4-morpholin-2-yl-phenyl)-[5-(2,2,2-trifluoro-ethoxy)-pyrimidin-2-yl]-amine; 
 ((R)-3-Chloro-4-morpholin-2-yl-phenyl)-(5-trifluoromethyl-pyrimidin-2-yl)-amine; 
 (R)-5-Chloro-N-(4-(morpholin-2-yl)phenyl)pyrazin-2-amine; and 
 a pharmaceutical active acid addition salt thereof. 
 
     
     
       24. The compound of  claim 6 , selected from the group consisting of
 (R)-6-Chloro-N-(4-(morpholin-2-yl)phenyl)pyrazin-2-amine; 
 (R)—N-(3-Fluoro-4-(morpholin-2-yl)phenyl)-5-(2,2-trifluoroethoxy)pyrimidin-2-amine; 
 (R)—N-(3-Fluoro-4-(morpholin-2-yl)phenyl)-4-(2,2,2-trifluoroethoxy)pyrimidin-2-amine; 
 (R)-5-Fluoro-N-(3-fluoro-4-(morpholin-2-yl)phenyl)-4-(2,2,2-trifluoroethoxy)pyrimidin-2-amine; 
 (R)-5-Chloro-N-(3-fluoro-4-(morpholin-2-yl)phenyl)pyrimidin-2-amine; and 
 ((R)-3-Chloro-4-morpholin-2-yl-phenyl)-[4-(2,2,2-trifluoro-ethoxy)-pyrimidin-2-yl]-amine; 
 or a pharmaceutically suitable acid addition salt thereof. 
 
     
     
       25. The compound of  claim 3 , wherein Y is —CH 2 —, —CH 2 CH 2 —, —CH(CF 3 )— or —CH(CH 3 )— and Ar is pyrimidinyl, pyrazolyl, benzothiazolyl, quinolinyl, quinazolinyl, benzo[d][1.3]dioxolyl, 5,6,7,8-tetrahydro-quinazolinyl or 1,3,4-oxadiazolyl. 
     
     
       26. The compound of  claim 25 , wherein said compound is
 (S)—N-((2-Chloroquinolin-3-yl)methyl)-4-(morpholin-2-yl)aniline; 
 or a pharmaceutically suitable acid addition salt thereof. 
 
     
     
       27. The compound of  claim 1 , wherein A is N, B is CH, Y is a bond and Ar is pyrimidinyl. 
     
     
       28. The compound of  claim 27 , wherein said compound is
 (RS)-5-Cyclopropyl-N-(5-(morpholin-2-yl)pyridin-2-yl)pyrimidin-2-amine. 
 
     
     
       29. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula I 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is hydrogen, lower alkyl, halogen, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by halogen, cyano, nitro, C 3-6 -cycloalkyl, —CH 2 —C 3-6 -cycloalkyl, —O—CH 2 —C 3-6 -cycloalkyl, —O—(CH 2 ) 2 —O-lower alkyl, S(O) 2 CH 3 , SF 5 , —C(O)NH-lower alkyl, phenyl, —O-pyrimidinyl, optionally substituted by lower alkoxy substituted by halogen, or is benzyl, oxetanyl or furanyl; 
         m is 1 or 2; 
         Ar is aryl or heteroaryl, selected from the group consisting of naphthyl, pyrimidinyl, benzothiazolyl, quinolinyl, quinazolinyl, benzo[d][1.3]dioxolyl, 5,6,7,8-tetrahydro-quinazolinyl, pyrazolyl, pyrazinyl, pyridazinyl, and 1,3,4-oxadiazolyl; 
         Y is a bond, —CH 2 —, —CH 2 CH 2 —, —CH(CF 3 )— or —CH(CH 3 )—; 
         R 2  is hydrogen or lower alkyl; 
         A is CR or N; and R is hydrogen, cyano, halogen or lower alkyl; 
         R′ is hydrogen or halogen; with the proviso that when R 1  is halogen, A is CH; 
         B is CH or N; 
         n is o, 1 or 2; and 
         X is a bond, —CH 2 — or —O—; 
         or a pharmaceutical active acid addition salt thereof 
         and a pharmaceutically acceptable carrier. 
       
     
     
       30. The compound of  claim 23  wherein said compound is N-(4-(morpholin-2-yl)phenyl)-5-(trifluoromethyl)pyrazin-2-amine or a pharmaceutical active acid addition salt thereof.